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pegr writes "Andrew 'bunnie' Huang, Reverse Engineer, XBox hacker, and generally smart guy, muses over the H1N1/swine flu virus as only a reverse engineer can: 'I now know how to modify the virus sequence to probably make it more deadly.' Not that he would, of course. bunnie has consistently made the esoteric available to us mere mortals, and his overview of the H1N1 virus is a fascinating read from a unique perspective." (Seen today also at the top of Schneier on Security.)

It would actually take less than that, though it wouldn't spread the same way. Remember that prions are proteins that can kill you rather than whole viruses. The protein that gets misfolded in Bovine Spongiform Encephalopathy (or mad cow) seems to be called just Prion protein [nih.gov] and is only 253 amino acids. If bunnie is correct and one amino acid = 6 bits, then thats 1,518 bits. "Bit calculator" [matisse.net] tells me that would be 0.185 kbytes.

Granted, this wouldn't be airborne death, would be extremely slow, and wouldn't cause a pandemic, but still, far less data.

Even if you were to go the viral route, at least one virus is tricky in that it produces multiple proteins from overlapping reading frames. [nih.gov] That is, the same sections of RNA genome (sendai uses RNA instead of DNA) is read in multiple ways to make different functional proteins, one protein might be formed from reading AUG GAU GGG CAG, which would make the amino acid sequence MDGQ, but that could aso be read as A UGG *AUG* GGC AG where the starred AUG is the start, making a protein of MG. I find that pretty cool, because as Carl Sagan pointed out, try doing that with english. "Romancement to get her" can be spaced differently to produce "roman cement together" is the longest he could come up with and it doesn't even make sense. Viruses make whole proteins that work. Anyway, the point of all that was that viruses can in some cases double up, so it would take even fewer nucleotides to produce the same amount of protiens.

The protein that gets misfolded in Bovine Spongiform Encephalopathy (or mad cow) seems to be called just Prion protein [nih.gov] and is only 253 amino acids. If bunnie is correct and one amino acid = 6 bits, then thats 1,518 bits.

So you're saying that it would take just 11 posts on Twitter to kill someone?

The coat proteins do more than just carry the DNA to your cells, they allow the virus to actually get inside the cell. That's a pretty major part of a virus, the DNA itself is not going to get inside a cell to produce an infection. There are also more proteins inside many viruses that are essential HIV has several for example. [doctorspiller.com] Influenza does too [respirator...sts.com.sg]. So it requires more than just the data to kill you.

Viroids [wikipedia.org] are infectious particles that are just nucleotides, just the data. All the viroids that we know of

Viral strains that are less deadly will reproduce for a longer time in the host before the host dies. In the case of HIV, that means the host will have more sexual partners, giving that less deadly strain more hosts to infect. This less deadly strain then has more hosts with a longer lifespan, developing a cycle of selective pressure upon HIV wherin those strains that are less virulent become more likely to reproduce.

While that's true, it's kind of stupid. You might as well say guns don't kill people, they shoot bullets that break important organs. Tuberculosis doesn't kill you, the lack of functioning lungs did. It wasn't that brain cancer that got you, it was the lack of a a cerebellum. Come on.

You started off strong enough, then held on ok for a bit, then lashed out at programmers, logic, and liberals while being apologetic at the same time and never really making a strong point other than when you got to your defense of philosophy as you see it at the end. All, in all, I give it a B-.
Now find your enter key and someone other than me might actually read that long son of a bitch of a paragraph you just shat out.

Did you just call the flu an unsuccessful virus? I dare you to show me two people in Europe or North America who never had it.

However, I'm still not afraid. TFA is right: this is one fast mutating virus. So much in fact, that every possible mutation has appeared already. I'm too lazy do back it up with math, but the numbers should be interesting.

Even if such a statement could be verified mathematically AND historically - we still haven't seen every possible mutation in every possible situation in which it might be spread. The world has never before seen the population density we see today. Virulant outbreaks can span the globe in a week or less. The people at CDC are concerned for a reason.

Never had it, or never experienced symptoms due to an immune system that squashes the bug before a symptom-causing response is necessary? unless you live in a bubble, I highly doubt you've never been immunized one way or the other.

It's not that big a stretch. I had the 'flu this year and I don't think I had ever been so sick for so long in my life. (It's fair to say I have been sicker, but only very briefly) Then I realised that every illness that I had previously called 'flu was merely a common cold.

OTOH, are you sure that your "dozen times since then" have been 'flu and not a common cold? I always knew there was a difference between the common cold and the 'flu, but it took me 45 years

Making a virus more 'deadly' is usually not very good for the virus. If it's host dies, so does it's habitat. Not to mention the host can no longer really spread it.

Be careful with that kind of thinking, because it's not strictly true. There's an oft-repeated saying that all diseases will naturally become less deadly over time because it doesn't pay to kill your host -- but in some cases it does pay.

Consider something like cholera. Cholera gives you horrific diarrhea and vomiting, and the resulting dehydration can kill you pretty quickly, especially if you're very young or otherwise infirm. Going by the above-stated theory, that would normally be bad -- except that cholera exists in all your excretions, and other people can catch it from coming into close contact with those excretions. What's more, the normal route of infection is via contaminated water supply -- so if your excretions can make it back to the water supply, more's the better for cholera. Who cares if you drop dead?

Similarly, malaria doesn't need you up and walking around to infect people. You can be lying on your deathbed and a mosquito can still fly in through the window, bite you, and then fly off and bite someone else. That's why, though malaria has been known since the dawn of human history, it never seems to become less of a health threat to humans. There's simply no evolutionary pressure in that direction.

True, neither cholera or malaria is caused by a virus. But I just wanted to point out that the "evolution favors keeping your host alive" theory is rather too simplistic for the bigger picture of human disease.

You're still assuming that "killing the host" happens some non-trivial amount of time after "infecting the host" -- at some point the host won't be able to travel far enough to infect anyone who wasn't also at risk from the original point of infection. Given modern travel speeds that threshold is pretty small, but it certainly still exists; a virus that killed people within 1 minute of infection would never make it out of the building where it was first encountered.

In your unrealistic example, yes you are correct. IN the real world the time you need to keep the host viable and be a year before symptoms emerge. As long as the host does whatever is needed to spread the virus, you will see virus growth.

For AIDS, you only need to have unprotected sex a few times and the virus will be successful. SO if you don't notice symton for a coupl of years, and you are sexually active, that's more then enough for the virus to propagate.

For AIDS, you only need to have unprotected sex a few times and the virus will be successful. SO if you don't notice symton for a coupl of years, and you are sexually active, that's more then enough for the virus to propagate.

Actually, AIDS is not considered a highly infectious disease. Seriously. If you're having unprotected vaginal sex, it might take a great many times before the virus is successfully transmitted from a woman to a man. Scientists believe the actual rate of infection in such cases may be less than 1 percent. Sooooooooo.... feel better? Wanna risk it? Didn't think so.

Unless you are creating a weapon... Obviously killing someone instantly would be worthless (just use a bomb), but if they could increase the mortality rate while maintaining the contagious period, then some crazy people might find it interesting.

The reason why they are scared aren't because it's ability to kill right now, the reason why they are scared and why you should be too is because:1. it spreads like wildfire - off season, imagine what kind of havoc this will do when the flu season starts.2. unlike most other, this will primarily hit young people, our immune system isn't geared for this, while this in the beginning wont cause many deaths, the consequences of having 20-30% of your working population off for a week or two due to sickness is re

Provided the pre-symptom incubation period is fairly long, a deadly virus CAN spread far and wide.

Let's say there's a flu mutation which has a 3-month incubation period, give or take a couple weeks. It has a mortality rate of 50%. However, we don't know about it until three months after the first couple infections - by which time it's likely that the majority of people who will catch it, have caught it. Voila, you've got a pandemic on your hands to which there is no prevention: it's only a matter of time un

Actually, for the Roman Empire one, he may be thinking of the Antonine Plague of 166 A.D., which may have wiped out up to a third of the population, and is believed to have been measles or more likely smallpox (both viruses). Still, I'm not sure if one pandemic outbreak is sufficient evidence for the success of a given disease on an evolutionary scale. After all, we were eventually able to wipe smallpox from the face of the Earth -- something we've tried doing to other diseases with only limited success --

If I were to speculate I would say that they are probably still around, just that many of those that didn't die had a higher resistance for that particular virus/disease; and that those people are our ancestors. That being said we also have things like hygiene now that might remove some of the factors contributing to a lower tolerance for diseases/viruses/etc.

> The second-most successful virus was the one that struck the> Roman Empire circa 600 A.D. because if that virus had not struck,> the Eastern Roman Emperor's army would have succeeded in his> mission to reclaim Italy, Rome, and possibly France/Gaul too.

Was this after Narses the court eunuch and general conquered Italy, then let the Lombards attack the North to show the Emperor that he was needed (and committed suicide in shame when they succeeded)?

>What did these viruses have in common? They were very virulent, killing the host quickly, but it didn't matter because their RNA code was spread via fleas.

Right, but the modern world, at least in wealthier countries, are fairly hygienic. I dont think Ive ever seen a flea outside the woods. For a virus to be successful in today's world it would probably need to keep the host alive a lot longer. Perhaps this is why we just arent seeing pandemics on this level since around we got a good understanding of ge

The most-successful virus struck Europe in the mid-1200s, killed 40% of the people, and created a shortage of labor that allowed the serfs to free themselves and demand pay. Thus the middle class was born.

What did these viruses have in common? They were very virulent, killing the host quickly, but it didn't matter because their RNA code was spread via fleas.

A number of people doubt the bacterial bubonic plague/rats/fleas explanation due to the rapid manner of spread of the disease. A viral haemorrhagic fever, possibly airborne, is given as a more likely alternative.

A number of people doubt the bacterial bubonic plague/rats/fleas explanation due to the rapid manner of spread of the disease. A viral haemorrhagic fever, possibly airborne, is given as a more likely alternative.

The rapid spread would have been in part due to refugees fleeing the infected areas, unaware that they were incubating the disease. The plague is also potentially airborne, spreading to the lungs in severe cases and thereby allowing direct transmission between humans, which would allow the refugees to infect locals very fast.

Also, the reason the Black Death is thought to have been caused by bubonic plague is that there are many contemporary illustrations and descriptions of the victims, and they look a lot like modern plague victims. In an admittedly brief search, I couldn't find any reference to VHF producing buboes. Any alternative cause for the Black Death would surely have to produce those in at least a very sizable proportion of cases.

If only biologists had thought of the idea of treating DNA/RNA sequences as data, and then analyzing their properties statistically and computationally, with an eye towards what effects different modifications to the sequences might be predicted to have. We might call this field something fancy like "biological informatics".

That said, it's a quite well-written tutorial-style article with engaging prose that tackles a number of the relevant issues. I just balked at the "reverse engineer takes on biology" angle, as if that were something biologists had never thought of.

That said, it's a quite well-written tutorial-style article with engaging prose that tackles a number of the relevant issues. I just balked at the "reverse engineer takes on biology" angle, as if that were something biologists had never thought of.

there are several instances in human history of inventions being developed independently in exactly at the same time.

this is far different than the sheer ignorance "max tedroom" displayed with his series of tubes speech.

I just balked at the "reverse engineer takes on biology" angle, as if that were something biologists had never thought of.

Interesting that you should say that - the traditional biologists, by and large, don't think of doing things like this. Bioinformatics is a catch-all for any number of different disciplines, all in relative infancy, and almost always pioneered by people outside the traditional biology arenas.

I studied biochemistry in college, with a ton of extra math, physics, and computer science. Then I did a PhD developing DNA diagnostics for flu (awarded by the chem department, but I was a full time programmer and part time bench chemist).

My first paper was applying Shannon informational entropy theory to big alignments of flu DNA to look for conserved regions. No one around me had a clue what the hell I was on about. The code I wrote for that paper is still used by the Flu Division at CDC.

The only place where this article went wrong was in assuming that traits are trivially mapped to sequences. In practice, it almost always turns out to be extremely non-trivial, and in flu it almost doesn't work at all (the biologist figured out the easy cases years ago). Never the less, most really good science starts with some assumption that looks to be extremely over-simplified, and turns out to be very predictive.

There is going to be a lot of room for hackers and coders in the biological sciences in coming years - computer science has solutions to problems the traditional biologists haven't even realized are problems yet. Data storage and retrieval to support high-throughput sequencing labs, new algorithms for large-scale data analysis, instrument networking for lab automation. The job postings will go up just as soon as the biologists figure out that they have a problem...

If only biologists had thought of the idea of treating DNA/RNA sequences as data, and then analyzing their properties statistically and computationally, with an eye towards what effects different modifications to the sequences might be predicted to have. We might call this field something fancy like "biological informatics".

Hahaha, I'm sure the biological informaticians are laughing their asses off. Kinda like we computer geeks did when the Not So Hon. Ted Stevens described the Internet as a "series of tubes".

Meanwhile, though, I'm really enjoying the analogies that "bunnie" draws between DNA/RNA and computer bits. You see, I know a thing or two about computer bits, and ports, and stuff like that. And I know that DNA encodes proteins. But I didn't make the connection the way "bunnie" does, with a simple statement like this:

If you thought of organisms as computers with IP addresses, each functional group of cells in the organism would be listening to the environment through its own active port. So, as port 25 maps specifically to SMTP services on a computer, port H1 maps specifically to the windpipe region on a human. Interestingly, the same port H1 maps to the intestinal tract on a bird. Thus, the same H1N1 virus will attack the respiratory system of a human, and the gut of a bird.

That's probably baby science to a biological informatician, just like mapping to port 25 is baby networking to many of us. But for me, it makes the concepts click.

Similarly, we all made fun of the "series of tubes" metaphor, without considering that for most of humanity, an electron is "the size and shape of a small pea" (Heinlein reference). If thinking of the Internet as a bunch of interconnected steampunk-style tubes that can get full (saturated bandwidth) helps a non-techie understand why they can't watch YouTube and play Halo at the same time... well, so much the better.

Yeah, I probably should've been nicer. =] The Slashdot summary is actually more objectionable than the article is: as you point out, the metaphors in the article are quite well done. If you don't view it as "l33t XBox hacker discovers how to haxx0r viruses", but instead as "engaging tech writer uses computer terminology to explain how viruses work", it's much better.

Actually you are right, unfortunately for us they still booting their operating systems and learning SQL syntax, they had much trouble to read and sequence the DNA, now have PB of data waiting to be analyzed, it will take some years, decade or even decades, pretty likely our generation will not see any major and useful results from this DNA biology as this is just the very beginning of the research.

Yeah, it's true that there's some pretty lame stuff on the bioinformatics side too--- especially the early stuff has a feel of "hey guys what is computer", with books like Beginning Perl for Biologists [oreilly.com].

Why not just call it "programming"? Whether you're writing code for machine made of sand (silicon) or chemicals should not matter one bit.

Probably for the same reason we separate mathematicians from physicists, and chemists from biologists. There's a lot of specificity in each field that makes specialization worthwhile. Sure, biology is 'just' macro-scale chemistry (which, in turn, is 'just' macro-scale physics), but there are special cases that only happen in cells, as well as a lot of things that never happen in cells.

That doesn't mean that it's a bad thing to have someone with a foot firmly in both fields (computational physics, or biochemistry), but specializing is what allows computer engineers to spend more time on transistors than proteins, while the bioinformatics students learn about RNA without needing to bother with JAVA.

Change 1 of the DNA base and the embryo cannot grow to completion. Change a base and a cancer can suddenly develop and go awry (for example, kill the apoptose system of the cells). Kill one bit in the mytochondrial DNA and you probably get the same. I am not a biologist , and I am sure there are a lot of redundant gene, but some might not.

The 26,000-some bit virus only exists in the context of a host that contains considerably more DNA information than that. To use the awful computer analogies, it's like running a 26K program on a 300MB interpreter system; the small program just calls some combination of really complex, pre-built functions that shouldn't be called in that combination.

And keep in mind that the 300MB interpreter is meaningless without the context in which it executes: some physical machine.

As we extinguish species by the ark load it's worth musing where all their on board viruses and bacterium will land when they jump ship onto a new species. Reminds me of the ship of sick sailors who landed in Italy with the first boat load of rats bearing the plague. Supposedly many of the viruses that now plague us have adapted to us by way of our domestic livestock, especially fowl. We may be setting the table for the little critters with our obsessive need for antibiotics and wiping all indoor surfaces d

Well of course they will have stronger immune systems, but will they get sick as much? Its kind of comparing someone active with strong bones compared to someone inactive with weaker bones. If the most activity you do is go up and down stairs, your risk of breaking a leg is probably less than someone who is into extreme sports, even if the person is healthier and has stronger bones than the person who does little activity.

That's not how it works. Viruses don't all-of-a-sudden start to mutate when they "need" to. They mutate all the time. If a virus could "jump ship" to another species, it is most likely to do that when its first host species is common, not when that species is going extinct.

Your post is an example of a bad analogy substituting for intelligence. That's a common mistake. It's sort of like when your car won't start...

Beneath your amusing impotent rage, it looks like you still don't understand. Let me explain: More viruses -> more mutations -> more likely to jump species. Therefore, a higher population of the original host animal means a higher probability of cross-species mutations.

Supposedly many of the viruses that now plague us have adapted to us by way of our domestic livestock, especially fowl. We may be setting the table for the little critters with our obsessive need for antibiotics

Trust me on this one: "Our obsessive need for antibiotics" isn't going to affect viruses in the slightest.

and wiping all indoor surfaces down with lethal cleaners.

If you're suggesting that disease pathogens get stronger when subjected to chemical microbicides, that's about as silly as suggesting we could breed a race of superhumans who are immune to poisoning by feeding people arsenic and letting the survivors breed.

The Swiss did some research and found that farm kids raised tending livestock had stronger immune systems than Swiss city kids raised in sanitized urban housing.

You'll have to clarify what that means. Does "stronger immune system" mean more antibodies were found in their bloodstreams? That just means they hav

Only if the firewall also performs deep packet inspection. Many bad critters (viruses/bacteria) enter the system by making our firewall(s) think they are innocuous by externally looking link other good critters. It is the payload that is the real problem. If we could teach the body to somehow read the payload before docking with the receptors we could be disease (contracted from viruses/bacteria) free.

Only if the firewall also performs deep packet inspection. Many bad critters (viruses/bacteria) enter the system by making our firewall(s) think they are innocuous by externally looking link other good critters. It is the payload that is the real problem. If we could teach the body to somehow read the payload before docking with the receptors we could be disease (contracted from viruses/bacteria) free.

Nanoprobe-supported organs. Once again, Star Trek has beaten us to it.

Not to mention a rather nifty virus scanner in the transporter buffer... Oh yeah and you can patch it too. They even unintentionally made a backup copy of commander Riker. It's easy when you can just throw out every crazy idea you got.

" 'I now know how to modify the virus sequence to probably make it more deadly.' "I have some serious doubt. Ignoring the fact that 'make it more deadly' is a bit(lot) vague, it's not a pile of bits.Also, there is a long way between designing a virus, and being able to make it.

OTOH, he does hack a trivial easy piece of hardware, so maybe he did it with dust tape, spit and MacGyvers seman.

Looking at the amino acid and codon table [algoart.com] I noticed another interesting point: The triples which code for the same amino acid typically differ only in the last base. Indeed, this can be made stronger: Except for the STOP codon, in each set of codons with no more than four members, the first two bases are always the same (for those with more than four codons that's of course not possible). Moreover, quite a few amino acids have exactly four codons which differ only in the last base, i.e. the amino acid is completely and unambiguously determined by the first two bases alone. Indeed, one can rearrange this into the following 16-entry table:

FTFA: As you can see, we have 'GAA' coding for 'E' (Glutamic acid). To modify this genome to be more deadly, we simply need to replace 'GAA' with one of the codes for Lysine ('K'), which is either of 'AAA' or 'AAG'.

Article author points out that TWO triplets both translate into Lysine. OP's ability to RTFA is bunk. Learn to not troll.

Although for many unwashed masses your ramblings look quasi-brilliant, your analysis has WAY too many holes. Each triplet is translated into ONE of TWENTY amino acids. You know what? Some triplets are translated to the SAME amino acids. Your analysis is bunk. Learn your biology.

Yes, each triplet is translated into one amino acid (OK, there are a few which are translated into none). There's no single triplet which is translated into two or more amino acids. The fact that several triplets are translated into the same amino acid doesn't change that (even if you shout). Learn your logic.

Actually, they had a control group who were given a placebo who also died even though they had not even been given the vaccine. Also, the researchers died and through luck these two groups were each the exact same size as the group given the vaccine, thus the 300% mortality rate.